In RNA interference (RNAi), an iRNA (an RNA molecule with gene interference activity) of appropriate sequence will down-regulate a given gene by preventing a specific messenger RNA (mRNA) from producing protein. RNAi has been rapidly developed into a potent and broadly applied tool in medicine, biofuels, agriculture and basic research (Sledz and Williams, Blood, 106(3):787-794 (2005)).
Production, packaging, storage and delivery of RNA remains the central challenge to the therapeutic application of RNAi technology. Purified RNAs are notoriously unstable and are extremely vulnerable to degradation, for example by nucleases, hydroxyl radicals, UV light, and Mg2+-mediated inline attack. The low-stability of RNAs precludes storage for long periods of time and severely limits the potential range of distribution and application methods for RNA-based pharmaceutical compounds. As a result, RNA-based applications commonly require costly and inefficient chemical modification of RNA for stabilization and delivery.
Therefore, it is an object of the invention to provide methods and compositions for the improved delivery of RNA to a target cell or a host.
It is still another object of the invention to provide methods and compositions for down-regulating gene expression in a host.